Several tissues including erythrocytes, bone marrow, and brain as well as the malaria parasite are dependent on exogenous, pre-formed purines. We have identified the liver as the major source of these compounds and adenosine as the chemical form supplied. The proposed study is an analysis of the factors which regulate adenosine export from liver and mechanisms by which this regulation is achieved. Studies will consist of (1) analysis of purines in hepatic blood in vivo; (2) analysis of the output from the isolated liver perfused with various potential regulatory compounds, and (3) determination of the intracellular intermediates under conditions of variable adenosine production (in order to indicate the rate-limiting step in its formation). These analyses are rendered feasible largely through the development in this laboratory of a sensitive microbiological assay. The investigation promises to elucidate a physiologic mechanism with important implications for several normal tissues and disease states, as diverse as gout, the Lesch-Nyhan syndrome, tumor growth, and malaria.